Aim: To report the precision of guided access cavity preparations in relation to demographical and dental variables in 50 patients. Methodology: This observational study was carried out during the period 2014–2017. The patients were consecutive referrals to a private endodontic practice. The inclusion criteria were as follows: (i) pulp space obliteration associated with signs of apical periodontitis (PAI score >3 or sensitive to percussion, (ii) teeth with pulp space obliteration in need of a post, where the referring dentist had attempted or failed to negotiate the obliterated root canal (and it was not possible to negotiate using the operating microscope within a reasonable time frame) and (iii) a surgical intervention was not justified. A published methodology for guided endodontics was used. Measures on demographical and previous dental history were analysed and related to drill path precision, being evaluated on radiographs as optimal (centre of the root canal) or acceptable (peripheral/tangential). The chi-square test was used for analyses of correlation between predictor variables and binary logistic regression analysis using backward elimination with degree of obliteration, guided access cavity preparation depth and precision as dependent variables. Significance level was 0.05. Results: Thirty-one female (median age 65 year) and 19 males (median age 69 year) were enrolled. Overall, 88% (n = 44) of the teeth had pulp space obliteration associated with signs of apical periodontitis, whereas the remaining teeth were in need of a post. The pulp space obliterations were longer in maxillary compared with mandibular teeth (P = 0.024). The performance of the drill path in mandibular teeth versus maxillary teeth resulted in a significantly greater number of optimal precision scores (P = 0.033), and when a previous attempt at access and canal negotiation had occurred versus no attempt (P = 0.009). Even in cases with the worst outcome, the technique was still successful clinically. Conclusions: The clinical implementation of guided root canal treatment in fifty serial cases of single-rooted teeth with pulp space obliteration was associated with a precision that in all cases led to the location and negotiation of the root canal and completion of the treatment.